Dr. Pauline Maki is featured in a documentary on PBS entitled “Hot Flash Havoc.” The documentary “sets the record straight about the U.S. government sanctioned Women's Health Initiative study released in 2002, which misrepresented that hormone replacement therapy — used by millions of women to treat the symptoms of menopause — could actually increase the risk of heart attacks and cancer.”3/21/2016

One of the primary focuses of Dr. Leah Rubin’s program of research is to better understand sex differences in psychosis through the exploration of hormonal contributions to this mental illness. This work is important given that the course of schizophrenia is more benign in women than in men and thus, sex differences in neuroendocrine, genetic and/or epigenetics factors may contribute to sex differences in clinical presentation and cognitive abilities. The goal of the research is to identify sex-specific, neurohormonal treatments for mental illness and to improve the lives of individuals with severe mental illness.

To date, Dr. Rubin’s work has yielded novel and important findings of sex differences in the impact of antipsychotic treatment on sexually dimorphic cognitive deficits in schizophrenia. The primary finding was that women and men differed in the cognitive benefits they derived from antipsychotic treatment. Other findings from her work are that high levels of peripheral oxytocin are protective across a broad range of clinical symptoms and emotion perception in women but not men with schizophrenia.

Oxytocin Alterations in Schizophrenia: Plasma levels and gene methylation in patients and relativesPI: Leah Rubin, PhDThe goal of this project was to investigate endogenous oxytocin and oxytocin receptor epigenetics in patients with schizophrenia, relatives and controls. This study was funded by a NARSAD Young Investigator Award from the Brain & Behavior Research Foundation from 2013-2015.

The Role of Endogenous Neurohormones in Modulating Clinical Symptoms, Social/Emotional and Cognitive Functioning in SchizophreniaBIRCWH Scholar: Leah Rubin, PhDThis mentored award focused on understanding how two sexually dimorphic neurohormones – oxytocin and vasopressin – may contribute to sex differences in schizophrenia. Dr. Rubin received this award in 2010. Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) is a women’s health research career development program at UIC. It is funded by a 10-year K12 institutional training grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (K12 HD055892-10).

Effects of Estrogen on Cognition in SchizophreniaPI: Leah Rubin, PhDThe goal of this mentored award was to identify neuroendocrine mechanisms that contribute to variations in cognitive function in schizophrenia. Specifically, Dr. Rubin aimed to characterize how individual variation in estrogen levels affected cognitive abilities that showed a sex difference. This study was funded by the National Institute of Mental Health (NIMH) from 2007-2009 (F31 MH082480).

Our research with HIV+ women has been aimed at understanding how different female-specific risk factors contribute to their cognitive and mental health. Studying HIV+ women is particularly important given that these women may be at greater risk for cognitive deficits/declines due to issues of underserved communities including poverty, low literacy levels, low educational attainment, substance abuse, mental health issues. In our Neurology publication (Maki, Rubin, et al. 2014), we demonstrated that HIV-infected women show a prominent deficit in verbal learning and memory and attention compared to at-risk HIV-uninfected (HIV-) women. Across multiple studies we have identified certain factors that are differentially associated with verbal learning and memory in HIV-infected compared to HIV-uninfected women including crack/cocaine use, menopausal anxiety, insulin resistance, and perceived stress. We have also shown that post-traumatic stress was associated with worse scores on tests of verbal learning, memory, and psychomotor speed, and our structural and functional imaging studies suggest that the prefrontal cortex plays a critical role in stress-related memory impairments in HIV+ women.

Women’s Interagency HIV Study (WIHS), Chicago ConsortiumPI: Mardge Cohen, MDSubcontract PI: Pauline Maki, PhDThe WIHS is a multi-site prospective epidemiology cohort study of women who either are infected with HIV or are at increased risk for acquiring HIV infection. The Chicago Consortium is a clinical research site. As a past head of the Neurocognitive Working Group (NCWG) of the Women’s Interagency HIV Study (WIHS), Dr. Pauline Maki directed the implementation of the largest longitudinal study of cognitive function in HIV-infected women and HIV-uninfected controls. Dr. Leah Rubin has worked to develop and apply sophisticated statistical approaches to elucidate the association between HIV status and cognition in women as well as identify risk factors for cognitive difficulties. These risk factors have including menopause, drug abuse, COMT, liver function, insulin resistance, C-C chemokine receptor type 2 (CCR2) on monocyte subsets, and age-related glucocorticoid resistance. The WIHS is primarily funded by the National Institute of Allergy and Infectious Diseases (NIAID - U01 AI034993).

Other WMHRP studies led by Dr. Maki within the WIHS cohort include:

Effects of Drug Use on White Matter Integrity in HIV+ womenThe goal of this study was to examine the effects of recent crack cocaine use on brain structure in HIV+ women (2009-2012)

Effects of Drug Use on Hippocampal Function in HIV+ womenThe goal of this study was to examine the effects of recent crack cocaine use on hippocampal function during performance of a verbal memory test in HIV+ women (2009-2012).

Genetic Predictors of Cognition and Mood in HIV+ WomenThis subcontract analyzed the influence of four common genetic polymorphisms - ESR1, COMT, CYP1A1, and BDNF – in relation to memory function and depressive symptoms in HIV positive women (2007-2009).

Cognition, Brain Function, and Affect in Midlife HIV+ Women: The Influence of MenopauseThis subcontract was for a pilot cross-sectional substudy to the Women’s Interagency HIV Study and aimed to better understand how age and menopause influence performance on cognitive tests, affect, and fMRI measures of brain function in midlife women with HIV (2004-2005).

Effects of Drug Use on Prefrontal Cortex Function in HIV+ WomenPI: Vanessa Meyer, PhDThis training grant sought to investigate the effects of HIV and recent illicit drug use on cognitive function in women. The general aim of the study was to better understand the interactive effects of HIV and recent crack cocaine use on cognitive function. This study was funded by the National Institute on Drug Abuse (NIDA) from 2010-2012 (F31 DA028573).

Genetic Predictors of Cognition in HIV+ WomenPI: Erin Sundermann, PhDThis training grant sought to identify genetic predictors of cognitive performance and brain dysfunction in HIV. The general aim of the study was to characterize the effect of a common polymorphism of the catechol- O-methyl transferase (COMT) gene, Val158Met, on cognition and brain function in midlife women with HIV. This study was funded by the National Institute of Mental Health (NIMH) from 2008-2011 (F31 MH083537).

The Women’s Mental Health Research Program has worked collaboratively with researchers and clinicians in OB/GYN to increase provider and systems capacity to detect, diagnose and treat perinatal anxiety and depressive disorders in our patients. The majority of women who receive perinatal care at the University of Illinois Hospital and Health Sciences System are low-income minorities and these women have significantly higher rates of perinatal depression compared to the rest of the population (Bennett et al., 2004). Our previous longitudinal work with pregnant women at UIC found that 39% of the women had depression at preconception, 36% during pregnancy, and 33% in the postpartum period (Rubin et al., 2011). The intended outcome of our perinatal mental health research is to increase awareness, reduce stigma and connect women to the care they need.

Healthy Behaviors in Women - Illinois MotherCare ProjectPI: Vesna Pirec, MD, PhDCo-I: Pauline Maki, PhDThe goal of this project was to develop, implement, evaluate and disseminate a model for integration of mental health and healthy eating into perinatal care clinic settings. Among the health issues linked closely with depression and posing substantial risks to women and their offspring, the most central is disordered eating. The project proposed to (1) develop a self-care tool and guided self-care process for women with perinatal depression and/or eating problems; (2) incorporate this self-care tool and process, along with evidence-based treatments, into a stepped-care disease management model that coordinates mental health care with prenatal care. This study was funded by the Health Resources and Services Administration (HRSA), Maternal and Child Health Bureau (MCHB) from 2009-2012 (H59MC09957).

InterAgency Agreement with HFSPI: Vesna Pirec, MD, PhDCo-I: Pauline Maki, PhDThe goal of this grant was to: 1) Deliver workshops on screening, assessment, and treatment of perinatal mental health issues across Illinois; 2) Maintain a national consultation service for providers with questions of perinatal mental health, and; 3) Create a perinatal mental health protocol, medication chart and provider tool kit. This study was funded by the Illinois Department of Healthcare and Family Services from 2011-2012.

For the past 20 years, Dr. Pauline Maki has led a program of NIH-funded research on cognition and brain function in aging women. This program examines the role of menopause, vasomotor symptoms (VMS), and hormonal fluctuations on neuropsychological test performance and functional and structural neuroimaging outcomes.

In the past decade, our understanding of the role of menopause stage and menopausal symptoms on cognitive function has greatly expanded. There is now increasing evidence from large-scale prospective studies that women both report increased memory complaints and perform worse on memory tests during the menopausal transition. Dr. Maki’s work demonstrates a significant relationship between subjective memory complaints and objective memory declines, and also shows considerable individual differences in this relationship, with some women reporting few memory complaints and performing well on memory tests, and others having significant complaints and significant impairment. Dr. Maki’s work has contributed to the understanding of the factors underlying these changes in memory. Although there is strong evidence that the vasomotor symptoms (VMS) women report are unrelated to memory performance, Dr. Maki and collaborators discovered that physiologic VMS, as measured with ambulatory skin conductance monitors, bear a strong relationship with memory performance. Women under-report physiological hot flashes by about 45%, so measuring physiologic VMS with monitors appears to be critical in unmasking the relationship between VMS and memory.

The Science of Thermoregulation and Vasomotor Symptoms: Possible New Targets for TreatmentPI: Pauline Maki, PhDThe purpose of this 2-day conference was to bring together diverse key researchers and menopause clinicians to review recent scientific advances in our understanding of 1) the mechanisms underlying hot flashes and night sweats; 2) the efficacy of nonhormonal treatments for these symptoms. This study was funded by the National Institute on Aging (NIA) from 2014-2016 (R13 AG048700-01).

Effects of Estradiol and Phytoestrogens on Stress ResponsivityPI: Pauline Maki, PhDThis study was a randomized, placebo-controlled trial comparing estradiol and soy supplements to placebo for the treatment of daily anxiety, stress responsivity, objective hot flashes, and cognition in perimenopausal women. This study was funded by the National Institute of Mental Health (NIMH) from 2009-2015 (R01 MH083782).

Botanical Menopausal Therapies Mechanisms of CNS ActionPI: Pauline Maki, PhDThis Career Award grant examined the mechanisms by which phytoestrogens and botanical therapies for menopausal symptoms affect CNS function. This study was funded by the National Center for Complementary & Alternative Medicine (NCCAM) from 2004-2009 (K01 AT002321).

Effects of Botanicals on Cognition in Midlife WomenPI: Pauline Maki, PhDThe goal of this study was to compare the effects of standard hormone therapy, Trifolium pratense and Cimicifuga racemosa on brain function in midlife women. This study was funded by the National Center for Complementary & Alternative Medicine (NCCAM) from 2004-2006 (R21 AT001868).

The Center for Dietary Supplemental Research - Botanical Dietary Supplements for Women’s HealthPI: Norman Farnsworth, PhDCo-I: Pauline Maki, PhDThe initial efforts of this study were to investigate the clinical safety and efficacy of botanicals used to treat women's health with particular emphasis on therapies for menopause. Additional studies addressed mechanisms of action, identification of active compounds, and characterization of metabolism, bioavailability and pharmacokinetics of active species contained in these botanicals.This study was funded by the National Center for Complementary & Alternative Medicine (NCCAM) from 1999-2004 (P50 AT000155).

Effects of Sex Steroid Hormones on Cognition and Brain FunctionPI: Pauline Maki, PhDThe goal of this project was to gain insight into the effects of sex steroid hormones on cognitive function involving three primary lines of research: 1) sex differences in cognitive function; 2) changes in cognition in relation to natural fluctuations in endogenous hormones; and 3) changes in cognition associated with exogenous hormone intervention. This study was funded by the National Institute on Aging (NIA) from 2001-2002 (Z01 AG000192-02).